1. Field of the Invention
This invention relates to a process for producing 1,4-benzohydroquinone derivatives expressed by the following chemical formula (I): ##STR1## (where R.sub.1 stands for hydrogen or an acyl group, and R.sub.2 stands for the following formula: ##STR2## where n is 0 or an integer of 1 to 11, and A and B stand for hydrogen or they may form valence bond to form a double bond between the two carbon atoms attached to A and B), that is, 2,3-dimethoxy-5-substituted 6-methyl-1,4-benzohydroquinone or monoester thereof.
2. Description of the Prior Art
The compounds (I) obtained according to the method of the present invention can be easily converted, if so desired, into quinone compounds expressed by the following chemical formula (II): ##STR3## (where R.sub.2 is defined above) by oxidizing the compound (I) through the process of hydrolysis. The compounds (II) are generally known as coenzyme Q, and of these compounds, the one in which A and B form valence bond to form a double bond and n = 9, that is, 2,3-dimethoxy-5-methyl-6-decaprenyl-1,4-benzoquinone [2,3-dimethoxy-5-methyl-6-(3',7',11',15',19',23',27',31',35',39'-decamethy ltetracontadicaene-2',6',10',14',18',22',26',30',34',38'-yl)-1,4-benzoquino ne] is known as coenzyme Q.sub.10. This substance has close relation to the electron transfer system in the organism and plays an important role for generation of energy, and it is expected to produce many clinical effects in medical and pharmaceutical uses. There are known several methods for synthesizing a series of quinone compounds represented by the said coenzyme Q.sub.10. For instance, 2,3-dimethoxy-6-methyl-1,4-benzohydroquinone or 1-monoacylate thereof and (iso)decaprenol or its reactive derivative are reacted in the presence of an acid condensation catalyst such as for example a protonic acid such as formic acid, sulfuric acid, hydrochloric acid, phosphoric acid or p-toluenesulfonic acid, a Lewis acid such as zinc chloride, aluminum chloride or boron trifluoride-ether complex, or mixture thereof, and the obtained condensation product is oxidized after subjecting it, if need be, to a hydrolytic treatment to thereby obtain the object material. (See Japanese Pat. Pub. Nos. 17513/1964, 17514/1964 and 3967/1971). However, each of these methods is poor in yield in the condensation step, so that the yield of the object quinone compound is very low: about 30% at the highest even in the case of crude products. Further, each of the acid catalysts used in these methods has strong corrosiveness and is liable to have a deleterious effect on the apparatus. Also, the eluted metal could contaminate the products. Thus, these methods have handicaps for industrial applications.
Moreover, the use of said type of catalysts necessitates the operations for neutralization and extraction in separating the object material from the obtained reaction products, and further, the material is wasted in great quantity in comparison with the amount of catalyst which is used at a high rate to the starting material. This is undesirable from the viewpoints of cost and pollution. Thus, each of the heretofore used methods for synthesis of the quinone compounds of the type contemplated has many difficult problems for industrial application.
Various attempts have been made for improving the yield in the condensation process, and there has been developed a method for producing the desired benzoquinone products at a high yield by combining 2,3-dimethoxy-5-methyl-6-halogeno-1,4-benzohydroquinone-1,4-dimethoxymethy lether or 1,4-diacetate with a .pi.-allyl type nickel complex expressed by the following formula (III): ##STR4## (where X stands for halogen, R.sub.2 is defined above, and the site - - - - indicates half-bonding while the site - - - - indicates double-bonding). (Japanese Pat. Pub. Nos. 25137/1972 and 85546/1973). However, this method, although capable of significantly improving the condensation yield, still has the problem that Ni(CO).sub.4 used in adjusting the .pi.-allyl type nickel complex (III) is virulent to the respiratory system, and also as such substance is gaseous, its treatment is difficult and troublesome for the industrial application.
With a view to working out a method capable of efficiently obtaining the quinone compounds expressed by the chemical formula (II), the present inventors have strived for improvement of the condensation process for efficiently and industrially obtaining the hydroquinone compounds which are the precursors of the quinone compounds which are the end products, and have reached the method of the present invention.